[Functional roles of LFA-1 involved in signal transduction for thymocyte activation].

ABSTRACT

The biological significance of the signals triggered by the interaction of cell surface expressed LFA-1 and ICAM-1 has been investigated in Con A and immobilized anti-CD3 mAb stimulated cultures. When added at the beginning of activation in the presence of Con A, soluble anti-LFA-1 and anti-ICAM-1 mAbs could strongly inhibit cell proliferation. Such inhibitory effect was also exhibited in the proliferative response of thymocytes to immobilized anti-CD 3 mAb activation. However, the soluble anti-LFA-1 mAb was unable to inhibit the proliferation of primed thymocytes preactivated with Con A for 24 h or of IL-1 + IL-2 activated fresh thymocytes. Anti-LFA-1 mAb could profoundly inhibit Con A-induced thymocytes to produce IL-2 and IL-6 and to reduce IL-2 receptor expression. By contrast, anti-LFA-immobilized on plastic plates together with immobilized anti-CD 3 mAbs or CD 3 cross-linking with LFA-1 by secondary antibodies resulted in an enhanced activation signals for thymocytes to proliferate compared with that activated by anti-CD 3 alone. Thus, mAb to LFA-1 is a functional molecule for thymocyte activation, mediating signals contributed to very early phases of signal transduction through TCR/CD 3 pathway, and that LFA-1 might provide a costimulatory signal for expression of IL-2 R and IL-2 production.